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Circulating miRNA as Biomarkers of Obesity

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Circulating miRNA as Biomarkers of Obesity
Circulating miRNA as Biomarkers of Obesity
1
Wells ,
A’drianne
Robert
Nicole
Amanda
Cruz Velasco-Gonzalez3, Melinda Sothern2, Jovanny Zabaleta1,4
1Stanley
2
Uddo ,
2
Pelligrino ,
S. Scott Cancer Center, 2Behavioral & Community Health Sciences, School of Public Health,
3Biostatistics, School of Public Health; 4Pediatrics, School of Medicine
Methodology
Background
Obesity is a major problem for girls in the U.S.A.
Baseline
Follow-up
Serum
Serum
Using miRNeasy
Mini Kit
Product is miRNA
Reverse
Transcription
Intra abdominal fat contributes to metabolic
disorders
Using TaqMan®
Small RNA Assay
Free fatty
acids
Secretion of
Adipokines
Inflammatory
Markers
Product is cDNA
Dyslipidaemia
High
Glucose
Increased
Metabolic
Disorder
Insulin
Resistance
Inflammation
microRNA are involved in several processes associated with obesity
Real-Time
PCR
Using TaqMan®
Small RNA Assay
Quantification of
Targeted miRNAs
miR-143: The first microRNA found to be associated with obesity. Guo Y.
(2012) MicroRNAome Comparison between Intramuscular and Subcutaneous Vascular
Stem Cell Adipogenisis. Page 1.
Increased miR-143 expression is associated with an elevated body
weight—impairs glucose metabolism. It is a potential target for the
treatment of obesity-associated diabetes. Jordan SD (2010) Obesity-induced
overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs
glucose metabolism. Page 434
miR-223: Has been found to be down regulated after weight loss. Miliagro FI
(2013) High-Throughput Sequencing of microRNAs in Peripheral Blood Mononuclear
Cells: Identification of Potential Weight Loss Biomarkers. Page 5
miR-221: Expression levels of miR-221 were positively correlated with BMI
(particularly in women) and fasting insulin concentrations. Meerson A (2013)
Human adipose microRNA-221 is upregulated in obesity and affects fat metabolism
downstream of leptin and TNF-α.
Aim:
•Standardize the technique for the extraction of
miRNA from serum
•Do a pilot analysis to compare the levels of miRNA
in obese AA adolescents before and after diet
intervention
Results
We observed a trend towards reduction in the
levels of miRNA in the follow up samples.
African American
Adolescents
miRNA
Extraction
Obesity is, in general, defined by the BMI
2
Arguello ,
miR-193a/b: miR-193a-3p and miR-193b-5p were negatively correlated
with BMI. Meerson A (2013) Human adipose microRNA-221 is upregulated in obesity
and affects fat metabolism downstream of leptin and TNF-α.
miR-133b: Has been associated with inflammation. Shows a down
regulation after exercise. Nielsen S (2010) Muscle specific microRNAs are
regulated by endurance exercise in human skeletal muscle.
Conclusions
Serum is a good source of miRNA for
global association studies.
Diet intervention has an effect on the
levels of the targeted miRNAs.
There was a general trend toward
reduction in the levels all miRNA.
miR-193a showed the biggest
decrease post intervention (p=0.04).
We may be able to reach more
significance if we increase the
number of samples analyzed.
Future Directions
Increase sample size.
Show a relationship with weight
loss and targeted miRNAs.
Expand research with exercise
intervention.
Deep sequencing to broaden the
amount of targeted miRNAs.
Acknowledgements
We are most grateful to all
participants in the study, the CTRC
nurses and the staff at the LSUHSC
Wellness Center
This work was supported in part by a
grant from the NCMHD
(P20MD004817) and by a grant by the
NIGMS (P20GM103501)
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